Pathogenesis of Giant Cell Arteritis and Takayasu Arteritis-Similarities and Differences

Abstract

Purpose of review: Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are auto-inflammatory and autoimmune diseases with a highly selective tissue tropism for medium and large arteries. In both diseases, CD4⁺ T cells and macrophages form granulomatous lesions within the arterial wall, a tissue site normally protected by immune privilege. Vascular lesions can be accompanied by an extravascular component, typically an intense hepatic acute phase response that produces well-known laboratory abnormalities, e.g., elevated ESR and CRP. It is unclear whether GCA and TAK lie on a spectrum of disease or whether they represent fundamentally different disease processes.

Recent findings: GCA and TAK share many clinical features, but there are substantial differences in genetics, epidemiology, disease mechanisms, response to treatment, and treatment complications that give rise to different disease trajectories. A significant difference lies in the composition of the wall-infiltrating immune cell compartment, which in TAK includes a significant population of CD8⁺ T cells as well as natural killer cells, specifying disparate disease effector pathways mediating tissue damage and vessel wall remodeling. Despite the similarities in tissue tropism and histomorphology, GCA and TAK are two distinct vasculitides that rely on separate disease mechanisms and require disease-specific approaches in diagnosis and management.

Keywords: Giant cell arteritis; Intimal hyperplasia; Macrophages; Neoangiogenesis; T cells; T regulatory cells; Takayasu arteritis; Vascular remodeling.

Figure 1.. Distribution patterns of medium and large vessel vasculitides

Takayasu arteritis (TAK) mainly affects the aorta and the primary branches of the thoracic and abdominal aorta. Almost all patients have aortitis. Giant cell arteritis (GCA) manifests primarily in the 2nd-5th branches of the aorta, including the pathognomic involvement of the temporal artery. Only a subset of GCA patients develops aortitis, predominantly of the thoracic aorta. Left subclavian artery stenosis imaged by CT angiography in a 29-year-old woman diagnosed with Takayasu arteritis. Contrast-enhanced CT scan showing arterial wall thickening in the thoracic aorta of a 66-year-old woman diagnosed with GCA.

Figure 2.. Histologic hallmarks of Takayasu aortitis and giant cell aortitis.

(A) Takayasu arteritis (TAK): Low power magnification showing intimal (I) thickening, medial (M) damage with alternating areas of inflammation and fibrosis and paucicellular adventitial fibrous expansion (H&E, x40). (B) Giant cell aortitis: Similar magnification showing similar intimal (I) and medial (M) changes, but less adventitial (A) thickening compared to TAK (H&E, x40). (C) Takayasu arteritis: Trichrome stain of same segment as panel (A) that highlights the adventitial component (Trichrome, x10). (D) Giant cell aortitis: Trichrome stain of same segment as panel (B) contrasting the adventitial remodeling (Trichrome, x10). (E) Elastic staining of TAK aortitis showing intimal thickening (I), marked disruption/loss of elastic fibers in the medial layer (yellow arrowhead) and adventitial fibrous thickening (A) (Elastic van Gieson, x400). (F) TAK aortitis containing granulomatous lesions composed of macrophages/histiocytes and lymphocytes (white arrows) surrounding necrotic medial tissue (white star) (H&E x200).

Figure 3.. Pathogenic Cell Populations in Takayasu arteritis (TAK) and giant cell arteritis (GCA).

TAK and GCA are both granulomatous arteritides; with granulomatous infiltrates occupying mostly the media, but also the adventitia. Multinucleated giant cells may or may not be part of the infiltrate and are often localized along fragmented elastic laminae. Cellular components of the granulomatous infiltrates are T cells and tissue macrophages (histocytes), but the composition of the infiltrating cell populations is disease-specific. The ratio of CD4/CD8 T cells is low in TAK and high in GCA. Also, TAK aortitis includes a higher proportion of NK cells, suggesting differences in inflammatory effector pathways.

Figure 4.. Differential diagnosis of aortitis

Aortic inflammation occurs in low frequency in a spectrum of autoimmune diseases (RA, SLE, Behcet’s disease, sarcoidosis, IgG4-related disease etc). Inflammatory aortic aneurysms preferentially affect the abdominal and infrarenal aorta. Dispersed inflammatory cells or organized lymphoid clusters can be seen in non-inflammatory vasculopathies, such as atherosclerotic disease, congenital vascular disease. Infectious origin of vessel wall inflammation needs to be considered, especially in immunocompromised hosts.